ArticlemAbs
Beyond affinity: selection of antibody variants with optimal biophysical properties and reduced immunogenicity from mammalian display libraries.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed.
- ASD: antigen-specific antibody database.mAbs · 2026Article
- Multi-objective antibody design and optimization using machine learning.Nature reviews bioengineering · 2026Article
- Rapid immunization and antibody redesign platform discovers broadly neutralizing antibodies against non-immunized SARS-CoV-2 variant.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Antibody-drug conjugates in colorectal cancer: advances in targeted delivery and personalized oncology.Frontiers in bioengineering and biotechnology · 2026Review
- Engineering mammalian protein secretion: Toward the convergence of high-throughput biology and computational methods.Cell systems · 2025Review
- Pharmacological considerations for next-generation protein therapeutics in cardiovascular disease.The Journal of pharmacology and experimental therapeutics · 2025Review
- Review
- Optimizing co-expression strategies for the simultaneous display and secretion of monoclonal antibodies in CHO cells.Scientific reports · 2025Article
- Fifty years of monoclonals: the past, present and future of antibody therapeutics.Nature reviews. Immunology · 2025Article
- Review
- A Targeted Integration-Based CHO Cell Platform for Simultaneous Antibody Display and Secretion.Antibodies (Basel, Switzerland) · 2025Article
- Navigating the future of gastric cancer treatment: a review on the impact of antibody-drug conjugates.Cell death discovery · 2025Review
- A single point mutation on FLT3L-Fc protein increases the risk of immunogenicity.Frontiers in immunology · 2025Article
- Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics.Nature reviews. Drug discovery · 2024Review
- Challenges and future perspectives for high-throughput chimeric antigen receptor T cell discovery.Current opinion in biotechnology · 2024Review
- Predictive Model Building for Aggregation Kinetics Based on Molecular Dynamics Simulations of an Antibody Fragment.Molecular pharmaceutics · 2024Article
- Molecular Dynamics Simulations Reveal How Competing Protein-Surface Interactions for Glycine, Citrate, and Water Modulate Stability in Antibody Fragment Formulations.Molecular pharmaceutics · 2024Article
- Human antibody polyreactivity is governed primarily by the heavy-chain complementarity-determining regions.Cell reports · 2024Article
- A case study of a bispecific antibody manufacturability assessment and optimization during discovery stage and its implications.Antibody therapeutics · 2024Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The early phase of protein drug development has traditionally focused on target binding properties leading to a desired mode of therapeutic action. As more protein therapeutics pass through the development pipeline; however, it is clear that non-optimal biophysical properties can emerge, particularly as proteins are formulated at high concentrations, causing aggregation or polyreactivity. Such late-stage "developability" problems can lead to delay or failure in traversing the development process. Aggregation propensity is also correlated with increased immunogenicity, resulting in expensive, late-stage clinical failures. Using nucleases-directed integration, we have constructed large mammalian display libraries where each cell contains a single antibody gene/cell inserted at a single locus, thereby achieving transcriptional normalization. We show a strong correlation between poor biophysical properties and display level achieved in mammalian cells, which is not replicated by yeast display. Using two well-documented examples of antibodies with poor biophysical characteristics (MEDI-1912 and bococizumab), a library of variants was created based on surface hydrophobic and positive charge patches. Mammalian display was used to select for antibodies that retained target binding and permitted increased display level. The resultant variants exhibited reduced polyreactivity and reduced aggregation propensity. Furthermore, we show in the case of bococizumab that biophysically improved variants are less immunogenic than the parental molecule. Thus, mammalian display helps to address multiple developability issues during the earliest stages of lead discovery, thereby significantly de-risking the future development of protein drugs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.